In response to RFA MH-04-005 we are proposing a 3-year study designed to link animal-learning and clinical investigations by examining fear acquisition, extinction, and context effects in a de novo fear conditioning paradigm in humans. This project represents the collaboration between basic scientists specializing in psychophysiology and animal learning (Scott Orr, Ph.D. and Mark Bouton, Ph.D.) and a clinical psychologist specializing in the exposure-based treatments for anxiety disorders (Michael Otto, Ph.D.). The goal is to extend advances in animal learning to the understanding of the acquisition and loss of de novo fears in humans with affective disorders. Of particular interest are individual differences in context effects, which may underlie the differential expression of fears after extinction. In addition to testing for the presence of context effects in anxiety disorders, our proposed research focuses attention on determinants of individual differences in conditionability. Features of this study of particular relevance to the RFA include: (1) collaboration between basic and clinical researchers, (2) application of advances in animal learning to the understanding of fear learning and extinction in humans, (3) examination of the influence of contextual factors on extinction, (4) examination of state and trait factors linked to extinction and context effects (risk factors for resistance to extinction), and (5) establishment of a de novo conditioning paradigm that, in future applications, will be useful for examining the linkage between laboratory conditioning and the outcome and durability of exposure-based treatments for the anxiety disorders. Conditionability will be assessed in a manner similar to the procedures used by Orr et al. (2000), but will include assessment of "renewal" effects in response to shifts in contexts. This innovation has important implications for understanding the mechanism behind differential response rates to exposure-based treatment in the anxiety disorders. The application hypothesizes that patients with an anxiety or mood disorder will demonstrate: (1) greater conditioning during acquisition, (2) slower loss during extinction, and (3) stronger renewal effects than the healthy control group. The application will also examine the correlates of these effects; specifically, whether the magnitudes of effects obtained are linked to the severity of anxiety and related traits, and whether these effects persist in patients who have recovered from their anxiety disorder.